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Purpose: To determine if adjuvant interstitial hyperthermia (HT) significantly improves survival of patients with glioblastoma undergoing brachytherapy boost after conventional radiotherapy., Methods and Materials: Adults with newly-diagnosed, focal, supratentorial glioblastoma < or = 5 cm in diameter were registered postoperatively on a Phase II/III randomized trial and treated with partial brain radiotherapy to 59.4 Gy with oral hydroxyurea. Those patients whose tumor was still implantable after teletherapy were randomized to brachytherapy boost (60 Gy at 0.40-0.60 Gy/h) +/- HT for 30 min immediately before and after brachytherapy. Time to progression (TTP) and survival from date of diagnosis were estimated using the Kaplan-Meier method., Results: From 1990 to 1995, 112 eligible patients were entered in the trial. Patient ages ranged from 21-78 years (median, 54 years) and KPS ranged from 70-100 (median, 90). Most commonly due to tumor progression or patient refusal, 33 patients were never randomized. Of the patients, 39 were randomized to brachytherapy ("no heat") and 40 to brachytherapy + HT ("heat"). By intent to treat, TTP and survival were significantly longer for "heat" than "no heat" (p = 0.04 and p = 0.04). For the 33 "no heat" patients and 35 "heat" patients who underwent brachytherapy boost, TTP and survival were significantly longer for "heat" than "no heat" (p = 0.045 and p = 0.02, respectively; median survival 85 weeks vs. 76 weeks; 2-year survival 31% vs. 15%). A multivariate analysis for these 68 patients adjusting for age and KPS showed that improved survival was significantly associated with randomization to "heat" (p = 0.008; hazard ratio 0.51). There were no Grade 5 toxicities, 2 Grade 4 toxicities (1 on each arm), and 7 Grade 3 toxicities (1 on "no heat" and 6 on the "heat" arm)., Conclusion: Adjuvant interstitial brain HT, given before and after brachytherapy boost, after conventional radiotherapy significantly improves survival of patients with focal glioblastoma, with acceptable toxicity.

Although interstitial brachytherapy appears to be effective in treating recurrent malignant gliomas, it has been studied less extensively in patients with newly diagnosed tumors. To examine the effect of this treatment when used at the time of primary diagnosis, we retrospectively reviewed the records of 88 patients who received temporary interstitial implants of 125I for newly diagnosed malignant gliomas. This brachytherapy was preceded by a course of external radiation therapy and followed, in some cases, by chemotherapy. The median duration of survival after the beginning of external radiation therapy was 87 weeks in patients with glioblastoma multiforme and 160 weeks in those with anaplastic gliomas. In 46% of patients with glioblastoma multiforme and 56% of those with anaplastic gliomas, a second operation was necessary to remove symptomatic radiation necrosis, recurrent tumor, or both. Our results support the conclusion that interstitial brachytherapy used at the primary diagnosis lengthens survival in selected patients with glioblastoma multiforme. However, the toxicity is significant in terms of the need for surgical resection of symptomatic necrosis. In patients with anaplastic gliomas, the toxicity associated with the treatment probably outweighs its advantages.

In an attempt to improve local control and survival over those achieved with brain implant alone, a Phase I/II study of interstitial thermoradiotherapy was undertaken for recurrent malignant gliomas and recurrent solitary brain metastases. Between June 1987 and September 1990, 49 tumors in 48 patients were treated with thermoradiotherapy, including 26 glioblastoma multiforme (GM), 16 anaplastic astrocytomas (AA), 4 adenocarcinomas, and 3 melanomas. Patient age ranged from 18 to 71 years and Karnofsky Performance Status from 40 to 90. Stereotactically implanted catheters were used for both hyperthermia and brachytherapy. Hyperthermia was administered immediately before and after brachytherapy, heating as much of the tumor as possible to 42.5 degrees C for 30 min using helical coil microwave antennas. High-activity iodine-125 sources delivered tumor doses of 32.6 to 63.3 Gy. Complications included reversible neurologic changes in 13 patients, 9 seizures, 4 infections, 1 deep venous thrombosis with pulmonary embolus, and 1 scalp burn. Eighteen patients underwent reoperation for tumor and/or necrosis. Follow-up ranged from 9 to 166+ weeks. The median follow-up for living patients with GM and AA was 37 weeks and 92 weeks, respectively. Actuarial median survival was 47 weeks for patients with GM. For patients with AA, actuarial survival was 65% at 18 months and median survival has not yet been reached. Multivariate analysis showed a strong correlation between freedom from local tumor progression and "T90" temperature or minimum tumor temperature. Interstitial brain thermoradiotherapy is now being evaluated in a randomized Phase II trial for previously untreated GM.

Between January 1980 and January 1988, 95 evaluable patients with recurrent, unifocal, supratentorial malignant gliomas were reirradiated with high-activity iodine-125 sources implanted directly into tumor in afterloaded, removable catheters using computerized tomography-directed stereotaxy. A tumor dose of 5270-15,000 cGy was delivered at a maximum distance of 0.5 cm from the rim of the contrast-enhancing mass seen on CT scans. The median survival for the 50 patients with anaplastic astrocytoma was 81 weeks and for 45 patients with glioblastoma multiforme it was 54 weeks. The 18- and 36-month survival rates for patients with anaplastic astrocytoma were 46% and 28%, respectively; the 18- and 36-month survival rates for patients with glioblastoma multiforme were 22% and 8%, respectively. Because of clinical deterioration, increasing steroid dependency, and increasing mass effect at the implantation site seen on CT scans, necrotic tissue was excised from 47 patients (49%) at craniotomy; in some patients, tumor was mixed with necrotic tissue. The survival of reoperated patients was significantly longer compared with patients who did not undergo this procedure. Serial determination of the Karnofsky Performance Score (KPS) showed that there was no significant deterioration for the group as a whole during the 6 months immediately after implantation. At 18 months, 33 of the patients were alive; KPS ranged between 50 to 90 (mean 79) and 67% were steroid dependent. At 36 months, 18 patients were alive; 17 patients were evaluable with KPS that ranged between 40 to 90 (mean 76) and 53% were steroid dependent. Eleven of the 17 evaluable long-term survivors had a KPS of 80 or higher with a mean of 87. Interstitial brachytherapy may provide long-term survival in selected patients with recurrent malignant gliomas who have been irradiated previously with conventional teletherapy. The quality of life in the majority of long-term survivors appears to be quite satisfactory. Further attempts to control tumor growth using this modality appear to be warranted.